The Detector System for the Stratospheric Kinetic Inductance Polarimeter (SKIP)

The Stratospheric Kinetic Inductance Polarimeter (SKIP) is a proposed balloon-borne experiment designed to study the cosmic microwave background, the cosmic infrared background and Galactic dust emission by observing 1133 square degrees of sky in the Northern Hemisphere with launches from Kiruna, Sweden. The instrument contains 2317 single-polarization, horn-coupled, aluminum lumped-element kinetic inductance detectors (LEKID). The LEKIDs will be maintained at 100 mK with an adiabatic demagnetization refrigerator. The polarimeter operates in two configurations, one sensitive to a spectral band centered on 150 GHz and the other sensitive to 260 and 350 GHz bands. The detector readout system is based on the ROACH-1 board, and the detectors will be biased below 300 MHz. The detector array is fed by an F/2.4 crossed-Dragone telescope with a 500 mm aperture yielding a 15 arcmin FWHM beam at 150 GHz. To minimize detector loading and maximize sensitivity, the entire optical system will be cooled to 1 K. Linearly polarized sky signals will be modulated with a metal-mesh half-wave plate that is mounted at the telescope aperture and rotated by a superconducting magnetic bearing. The observation program consists of at least two, five-day flights beginning with the 150 GHz observations.Comment: J Low Temp Phys DOI 10.1007/s10909-013-1014-3 The final publication is available at link.springer.co

A LEKID-based CMB instrument design for large-scale observations in Greenland

We present the results of a feasibility study, which examined deployment of a ground-based millimeter-wave polarimeter, tailored for observing the cosmic microwave background (CMB), to Isi Station in Greenland. The instrument for this study is based on lumped-element kinetic inductance detectors (LEKIDs) and an F/2.4 catoptric, crossed-Dragone telescope with a 500 mm aperture. The telescope is mounted inside the receiver and cooled to $<\,4$ K by a closed-cycle $^4$He refrigerator to reduce background loading on the detectors. Linearly polarized signals from the sky are modulated with a metal-mesh half-wave plate that is rotated at the aperture stop of the telescope with a hollow-shaft motor based on a superconducting magnetic bearing. The modular detector array design includes at least 2300 LEKIDs, and it can be configured for spectral bands centered on 150~GHz or greater. Our study considered configurations for observing in spectral bands centered on 150, 210 and 267~GHz. The entire polarimeter is mounted on a commercial precision rotary air bearing, which allows fast azimuth scan speeds with negligible vibration and mechanical wear over time. A slip ring provides power to the instrument, enabling circular scans (360 degrees of continuous rotation). This mount, when combined with sky rotation and the latitude of the observation site, produces a hypotrochoid scan pattern, which yields excellent cross-linking and enables 34\% of the sky to be observed using a range of constant elevation scans. This scan pattern and sky coverage combined with the beam size (15~arcmin at 150~GHz) makes the instrument sensitive to $5 < \ell < 1000$ in the angular power spectra

The prevalence and incidence of mental ill-health in adults with autism and intellectual disabilities

The prevalence, and incidence, of mental ill-health in adults with intellectual disabilities and autism were compared with the whole population with intellectual disabilities, and with controls, matched individually for age, gender, ability-level, and Down syndrome. Although the adults with autism had a higher point prevalence of problem behaviours compared with the whole adult population with intellectual disabilities, compared with individually matched controls there was no difference in prevalence, or incidence of either problem behaviours or other mental ill-health. Adults with autism who had problem behaviours were less likely to recover over a two-year period than were their matched controls. Apparent differences in rates of mental ill-health are accounted for by factors other than autism, including Down syndrome and ability level

Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters

Multi‐dimensional biodiversity hotspots and the future of taxonomic, ecological and phylogenetic diversity: A case study of North American rodents

AimWe investigate geographic patterns across taxonomic, ecological and phylogenetic diversity to test for spatial (in)congruency and identify aggregate diversity hotspots in relationship to present land use and future climate. Simulating extinctions of imperilled species, we demonstrate where losses across diversity dimensions and geography are predicted.LocationNorth America.Time periodPresent day, future.Major taxa studiedRodentia.MethodsUsing geographic range maps for rodent species, we quantified spatial patterns for 11 dimensions of diversity: taxonomic (species, range weighted), ecological (body size, diet and habitat), phylogenetic (mean, variance, and nearest‐neighbour patristic distances, phylogenetic distance and genus‐to‐species ratio) and phyloendemism. We tested for correlations across dimensions and used spatial residual analyses to illustrate regions of pronounced diversity. We aggregated diversity hotspots in relationship to predictions of land‐use and climate change and recalculated metrics following extinctions of IUCN‐listed imperilled species.ResultsTopographically complex western North America hosts high diversity across multiple dimensions: phyloendemism and ecological diversity exceed predictions based on taxonomic richness, and phylogenetic variance patterns indicate steep gradients in phylogenetic turnover. An aggregate diversity hotspot emerges in the west, whereas spatial incongruence exists across diversity dimensions at the continental scale. Notably, phylogenetic metrics are uncorrelated with ecological diversity. Diversity hotspots overlap with land‐use and climate change, and extinctions predicted by IUCN status are unevenly distributed across space, phylogeny or ecological groups.Main conclusionsComparison of taxonomic, ecological and phylogenetic diversity patterns for North American rodents clearly shows the multifaceted nature of biodiversity. Testing for geographic patterns and (in)congruency across dimensions of diversity facilitates investigation into underlying ecological and evolutionary processes. The geographic scope of this analysis suggests that several explicit regional challenges face North American rodent fauna in the future. Simultaneous consideration of multi‐dimensional biodiversity allows us to assess what critical functions or evolutionary history we might lose with future extinctions and maximize the potential of our conservation efforts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154236/1/geb13050.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154236/2/geb13050_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154236/3/geb13050-sup-0001-Supinfo1.pd

Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective

Type II DNA topoisomerases (topos) are essential and ubiquitous enzymes that perform important intracellular roles in chromosome condensation and segregation, and in regulating DNA supercoiling. Eukaryotic topo II, a type II topoisomerase, is a homodimeric enzyme that solves topological entanglement problems by using the energy from ATP hydrolysis to pass one segment of DNA through another by way of a reversible, enzyme-bridged double-stranded break. This DNA break is linked to the protein by a phosphodiester bond between the active site tyrosine of each subunit and backbone phosphate of DNA. The opening and closing of the DNA gate, a critical step for strand passage during the catalytic cycle, is coupled to this enzymatic cleavage/religation of the backbone. This reversible DNA cleavage reaction is the target of a number of anticancer drugs, which can elicit DNA damage by affecting the cleavage/religation equilibrium. Because of its clinical importance, many studies have sought to determine the manner in which topo II interacts with DNA. Here we highlight recent single-molecule fluorescence resonance energy transfer and crystallographic studies that have provided new insight into the dynamics and structure of the topo II DNA gate

Reconstruction of ancient microbial genomes from the human gut

Loss of gut microbial diversity1–6 in industrial populations is associated with chronic diseases7, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000–2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.Ethics Overview of samples Reference-based taxonomic composition De novo genome reconstruction Methanobrevibacter smithii tip dating Functional genomic analysis Discussion Online content Method

aristotle's demonstrative logic

Demonstrative logic, the study of demonstration as opposed to persuasion, is the subject of Aristotle's two-volume Analytics. Many examples are geometrical. Demonstration produces knowledge (of the truth of propositions). Persuasion merely produces opinion. Aristotle presented a general truth-and-consequence conception of demonstration meant to apply to all demonstrations. According to him, a demonstration, which normally proves a conclusion not previously known to be true, is an extended argumentation beginning with premises known to be truths and containing a chain of reasoning showing by deductively evident steps that its conclusion is a consequence of its premises. In particular, a demonstration is a deduction whose premises are known to be true. Aristotle's general theory of demonstration required a prior general theory of deduction presented in the Prior Analytics. His general immediate-deduction-chaining conception of deduction was meant to apply to all deductions. According to him, any deduction that is not immediately evident is an extended argumentation that involves a chaining of intermediate immediately evident steps that shows its final conclusion to follow logically from its premises. To illustrate his general theory of deduction, he presented an ingeniously simple and mathematically precise special case traditionally known as the categorical syllogisti